Objective To evaluate the extent to which circulating biomarker and supplements of vitamin D are associated with mortality from cardiovascular, cancer, or other conditions, under various circumstances. Design Systematic review and meta-analysis of observational studies and randomised controlled trials. Data sources Medline, Embase, Cochrane Library, and reference lists of relevant studies to August 2013; correspondance with investigators. Study selection Observational cohort studies and randomised controlled trials in adults, which reported associations between vitamin D (measured as circulating 25-hydroxyvitamin D concentration or vitamin D supplement given singly) and cause specific mortality outcomes. Data extraction Data were extracted by two independent investigators, and a consensus was reached with involvement of a third. Study specific relative risks from 73 cohort studies (849 412 participants) and 22 randomised controlled trials (vitamin D given alone versus placebo or no treatment; 30 716 participants) were meta-analysed using random effects models and were grouped by study and population characteristics. Results In the primary prevention observational studies, comparing bottom versus top thirds of baseline circulating 25-hydroxyvitamin D distribution, pooled relative risks were 1.35 (95% confidence interval 1.13 to 1.61) for death from cardiovascular disease, 1.14 (1.01 to 1.29) for death from cancer, 1.30 (1.07 to 1.59) for non-vascular, non-cancer death, and 1.35 (1.22 to 1.49) for all cause mortality. Subgroup analyses in the observational studies indicated that risk of mortality was significantly higher in studies with lower baseline use of vitamin D supplements_. In randomised controlled trials, relative risks for all cause mortality were 0.89 (0.80 to 0.99) for vitamin D₃ supplementation and 1.04 (0.97 to 1.11) for vitamin D₂ supplementation_. The effects observed for vitamin D₃ supplementation remained unchanged when grouped by various characteristics. However, for vitamin D₂ supplementation, increased risks of mortality were observed in studies with lower intervention doses and shorter average intervention periods. Conclusions Evidence from observational studies indicates inverse associations of circulating 25-hydroxyvitamin D with risks of death due to cardiovascular disease, cancer, and other causes. Supplementation with vitamin D₃ significantly reduces overall mortality among older adults; however, before any widespread supplementation, further investigations will be required to establish the optimal dose and duration and whether vitamin D₃ and D₂ have different effects on mortality risk.

Context: The 2011 American Heart Association guidelines identified pregnancy complications as a risk factor for cardiovascular disease in women. However, miscarriage was not mentioned within the guidelines, and there is no consensus on the association between miscarriage and future risk of cardiovascular disease. Objective: To confirm or refute the association, a meta-analysis of published papers was conducted. Data sources: PubMed, Web of Knowledge and Scopus were systematically searched to identify appropriate articles. Reference lists were then hand searched for additional relevant titles. Study Selection: To be included, articles had to assess the association between miscarriage and subsequent cardiovascular disease in otherwise healthy women. Only women who had miscarriages were considered exposed. Pooled association measures, using random effects meta-analysis, were calculated for coronary heart disease and cerebrovascular disease. Publication bias and between-study heterogeneity were evaluated. Data Extraction: Two authors individually reviewed all studies and extracted data on patient and study characteristics along with cardiovascular outcomes. Results: 10 studies were identified, with 517 504 individuals included in the coronary heart disease meta-analysis and 134 461 individuals in the cerebrovascular disease analysis. A history of miscarriage was associated with a greater odds of developing coronary heart disease, OR (95% CI) =1.45 (1.18 to 1.78), but not with cerebrovascular disease, OR=1.11 (0.72 to 1.69). There was a strong association between recurrent miscarriage and coronary heart disease OR=1.99 (1.13 to 3.50). Evidence was found for moderate between-study heterogeneity and publication bias in the coronary heart disease analysis. Conclusions: The meta-analysis indicates that a history of miscarriage or recurrent miscarriage is associated with a greater risk of subsequent coronary heart disease.

Background: Inconsistent findings have been found among studies evaluating the risk of cardiovascular disease for women who have had pregnancies complicated by gestational hypertension (the new onset of high blood pressure without proteinuria during pregnancy). We provide a comprehensive review of studies to quantify the association between gestational hypertension and cardiovascular events in women. Methods and Results: We conducted a systematic search of PubMed, Embase, and Web of Science in March 2019 for studies examining the association between gestational hypertension and any cardiovascular event. Two reviewers independently assessed the abstracts and full‐text articles. Study characteristics and the relative risk (RR) of cardiovascular events associated with gestational hypertension were extracted from the eligible studies. Where appropriate, the estimates were pooled with inverse variance weighted random‐effects meta‐analysis. A total of 21 studies involving 3 60 1192 women (127 913 with gestational hypertension) were identified. Gestational hypertension in the first pregnancy was associated with a greater risk of overall cardiovascular disease (RR, 1.45; 95% CI, 1.17–1.80) and coronary heart disease (RR, 1.46; 95% CI, 1.23–1.73), but not stroke (RR, 1.26; 95% CI, 0.96–1.65) or thromboembolic events (RR, 0.88; 95% CI, 0.73–1.07). Women with 1 or more pregnancies affected by gestational hypertension were at greater risk of cardiovascular disease (RR, 1.81; 95% CI, 1.42–2.31), coronary heart disease (RR, 1.83; 95% CI, 1.33–2.51), and heart failure (RR, 1.77; 95% CI, 1.47–2.13), but not stroke (RR, 1.50; 95% CI, 0.75–2.99). Conclusions: Gestational hypertension is associated with a greater risk of overall cardiovascular disease, coronary heart disease, and heart failure. More research is needed to assess the presence of a dose–response relationship between gestational hypertension and subsequent cardiovascular disease. Registration: URL: https://www.crd.york.ac.uk/prosp​ero/ ; Unique identifier: CRD 42018119031.

Background: Both statins and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors lower blood low-density lipoprotein cholesterol levels to reduce risk of cardiovascular events. To assess potential differences between metabolic effects of these 2 lipid-lowering therapies, we performed detailed lipid and metabolite profiling of a large randomized statin trial and compared the results with the effects of genetic inhibition of PCSK9, acting as a naturally occurring trial. Methods: Two hundred twenty-eight circulating metabolic measures were quantified by nuclear magnetic resonance spectroscopy, including lipoprotein subclass concentrations and their lipid composition, fatty acids, and amino acids, for 5359 individuals (2659 on treatment) in the PROSPER (Prospective Study of Pravastatin in the Elderly at Risk) trial at 6 months postrandomization. The corresponding metabolic measures were analyzed in 8 population cohorts (N=72 185) using PCSK9 rs11591147 as an unconfounded proxy to mimic the therapeutic effects of PCSK9 inhibitors. Results: Scaled to an equivalent lowering of low-density lipoprotein cholesterol, the effects of genetic inhibition of PCSK9 on 228 metabolic markers were generally consistent with those of statin therapy ( R ² =0.88). Alterations in lipoprotein lipid composition and fatty acid distribution were similar. However, discrepancies were observed for very-low-density lipoprotein lipid measures. For instance, genetic inhibition of PCSK9 had weaker effects on lowering of very-low-density lipoprotein cholesterol compared with statin therapy (54% versus 77% reduction, relative to the lowering effect on low-density lipoprotein cholesterol; P =2×10 ^-7 for heterogeneity). Genetic inhibition of PCSK9 showed no significant effects on amino acids, ketones, or a marker of inflammation (GlycA), whereas statin treatment weakly lowered GlycA levels. Conclusions: Genetic inhibition of PCSK9 had similar metabolic effects to statin therapy on detailed lipid and metabolite profiles. However, PCSK9 inhibitors are predicted to have weaker effects on very-low-density lipoprotein lipids compared with statins for an equivalent lowering of low-density lipoprotein cholesterol, which potentially translate into smaller reductions in cardiovascular disease risk.

Mobile and tablet apps, ubiquitous and pervasive computing, wearable computing and domotics for health.

American Indian communities are at greater risk of hypertension and cardiovascular disease than the general US population and are exposed to greater cadmium levels. However, cadmium's effect on blood pressure is unclear. This study assesses the association between baseline urinary cadmium and longitudinal changes in blood pressure in American Indian communities. Cadmium was measured in 3047 baseline urine samples from Strong Heart Study participants from three geographic areas. Longitudinal changes in blood pressure across three study visits (1989-1999) were modeled using linear mixed models by baseline log urinary cadmium to creatinine ratio. Hypertension risk was evaluated using interval-censored survival analysis. Higher levels of urinary cadmium at baseline were associated with faster rates of increase in diastolic and systolic blood pressure (P [trend] = .001 and .02, respectively). The estimated change in diastolic and systolic blood pressures per year was 0.18 mm Hg (0.05-0.31) and 0.62 mm Hg (0.37-0.87) in the upper quintile of cadmium level compared with -0.11 mm Hg (-0.24 to 0.02) and 0.21 mm Hg (-0.04 to 0.46) in the lowest, respectively. A one-unit increase in log-transformed urinary cadmium was associated with 10% greater hypertension risk (95% confidence interval: 1.01-1.20). In conclusion, blood pressure of individuals with greater baseline levels of urinary cadmium increased at a faster rate relative to those with lower levels.